Long term evolution of a coincident ACTH-dependent and independent Cushing’s syndrome
Claudia Nogueira1,2, Eduardo Vinha1, Josue Pereira1,2, Ines Bernardes1, Taveira Gomes1,2, Joana Pardal1, Herberto Bettencourt1 & Davide Carvalho1,2
Author affiliations
1Sao Joao Hospital, Porto, Portugal; 2Faculty of Medicine, Oporto University, Porto, Portugal.
Introduction: The coexistence of Cushing’s disease with an ACTH-secreting adrenal adenoma is not frequent.
Case report: A 32-year-old woman was observed in our Department in 2000 for obesity. Hypercortisolism was documented and the basal hormonal study and functional testing oriented towards a pituitary origin (ACTH 24.8 pg/ml). Pituitary magnetic resonance imaging (MRI) showed an asymmetric pituitary gland and a pituitary stalk deviation to the left. Adrenal computerized tomography (CT) revealed a nodule in the right gland sized 1.5 cm. Inferior petrosal sinus sampling demonstrated a center to periphery ACTH gradient >3 before and after CRH. The patient abandoned the appointment and returned 6 years later complaining of weight gain, facial plethora and fatigue. The basal hormonal study and functional testing confirmed ACTH-dependent Cushing’s syndrome (ACTH 11.4 pg/ml) and the pituitary MRI showed a right-sided microadenoma. The patient was submitted to transsphenoidal resection in 2008 and histology confirmed an ACTH-secreting adenoma. However, hypercortisolism persisted. Pituitary MRI showed no adenoma. ACTH level 1 year after surgery was 7.6 pg/ml and showed no significant increase after CRH. Adrenal CT revealed a 2.5 cm adenoma on the right gland and a normal left gland. Adrenalectomy was performed in 2010 and histology revealed a cortical adrenal adenoma. There was resolution of hypercortisolism and the patient is on replacement therapy with hydrocortisone.
Conclusion: Whether an adrenal adenoma coexisted with a pituitary adenoma from the beginning or an autonomous adrenal adenoma after ACTH-induced-hyperpladia developed after longstanding stimulation by a pituitary ACTH adenoma, we don’t know. Investigations show that suppressed ACTH secretion in patients with Cushing’s syndrome results in reduction of the ACTH receptor mRNA expression in nonneoplastic adrenocortical cells. However, the regulatory mechanism of ACTH-R expression might be different in adenoma and persistent expression of ACTH-R alone might play a role in the autonomous production of cortisol.